A case of retinoblastoma resulting in phthisis bulbi after proton beam radiation therapy.

Purpose: Proton beam radiation therapy (PBRT) is a treatment option for advanced retinoblastoma (RB) resistant to chemotherapy and focal ophthalmic treatment. Here we report a case of RB with phthisis bulbi following PBRT. Observations: A 16-day-old boy with a family history of RB was referred to our institution. Initial examination revealed an extensive white mass in the right eye and a small tumor near the optic disk of the left eye. The patient was diagnosed with bilateral RB and treated with chemotherapy and focal ophthalmic therapy. The right eye showed shrinkage in the treatment course. The tumor control was not achieved bilaterally, and, therefore, PBRT was performed to preserve the eyes. However, the right eye became significantly phthisical following PBRT and ultimately required enucleation. Conclusions and importance: PBRT for RB may result in phthisis bulbi. Further investigations of its role and possible complications are warranted.

Effect of hyperthermia and proton beam radiation as a novel approach in chordoma cells death and its clinical implication to treat chordoma.

PURPOSE: Chordoma is a locally aggressive tumor that most commonly affects the base of the skull/clivus, cervical, and sacral spine. Conventional radiotherapy (RT), cannot be safely increased further to improve disease control due to the risk of toxicity to the surrounding critical structures. Tumor-targeted hyperthermia (HT) combined with Proton Beam Radiation Therapy (PBRT) is known to act as a potent radiosensitizer in cancer control. In this study, we investigated whether PBRT efficacy for chordoma can be enhanced in combination with HT as a radiosensitizer. MATERIAL AND METHODS: Human chordoma cell lines, U-CH2 and Mug-chor1 were treated in vitro with HT followed by PBRT with variable doses. The colony-forming assay was performed, and dose-response was characterized by linear-quadratic model fits. HSP-70 and Brachyury (TBXT) biomarkers for chordoma aggression levels were quantified by western blot analysis. Gene microarray analysis was performed by U133 Arrays. Pathway Analysis was also performed using IPA bioinformatic software. RESULTS: Our findings in both U-CH2 and Mug-Chor1 cell lines demonstrate that hyperthermia followed by PBRT has an enhanced cell killing effect when compared with PBRT-alone (p < .01). Western blot analysis showed HT decreased the expression of Brachyury protein (p < .05), which is considered a biomarker for chordoma tumor aggression. HT with PBRT also exhibited an RT-dose-dependent decrease of Brachyury expression (p < .05). We also observed enhanced HSP-70 expression due to HT, RT, and HT + RT combined in both cell lines. Interestingly, genomic data showed 344 genes expressed by the treatment of HT + RT compared to HT (68 genes) or RT (112 genes) as individual treatment. We also identified activation of death receptor and apoptotic pathway in HT + RT treated cells. CONCLUSION: We found that Hyperthermia (HT) combined with Proton Beam Radiation (PBRT) could significantly increase chordoma cell death by activating the death receptor pathway and apoptosis which has the promise to treat metastatic chordoma.

Particle Beam Radiation Therapy for Skull Base Sarcomas.

Background: To report the clinical experience of carbon-ion and proton radiation therapy for skull base sarcomas. Methods: An analysis of the retrospective data registry from the Shanghai Proton and Heavy Ion Center for patients with skull base sarcomas was conducted. The 1-/2-year local relapse-free, distant metastasis-free, progression-free, and overall survival (LRFS, DMFS, PFS, OS) rates as well as associated prognostic indicators were analyzed. Radiotherapy-induced acute and late toxicities were summarized. Results: Between 7/2014 and 5/2019, 62 patients with skull base sarcomas of various subtypes received carbon-ion radiation therapy (53), proton radiation therapy (5), or proton radiation therapy + carbon-ion boost (4). With a median follow-up of 20.4 (range 2.73-91.67) months, the 1-/2-year OS, LRFS, DMFS, and PFS rates were 91.2%/80.2%, 89.2%/80.2%, 86.0%/81.1%, and 75.8%/62.9%, respectively. Grade 3 mucositis and grade 4 hemorrhage were observed in 1 patient for each. Only grade 1 and grade 2 toxicities were observed except for the same patient with grade 4 acute toxicity died of severe hemorrhage (grade 5). Multivariate analyses revealed the lack of prior RT was an independent favorable prognostic factor for OS, PFS, and LRFS, age under 40 was associated with improved OS, early T-disease (T1/2) showed a significant association with better PFS. Conclusion: With few observed acute and late toxicities, particle beam radiation therapy provided effective tumor control and overall survival for patients with skull base sarcomas.

Effects on Periocular Tissues after Proton Beam Radiation Therapy for Intraocular Tumors.

BACKGROUND: To present our experience on orbital and periorbital tissue changes after proton beam radiation therapy (PBRT) in patients with intraocular tumors, apart from treatment outcomes and disease control. METHODS: Medical records of 6 patients with intraocular tumors who had been treated with PBRT and referred to oculoplasty clinics of two medical centers (Seoul National University Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center) from October 2007 to September 2014 were retrospectively reviewed. The types of adverse effects associated with PBRT, their management, and progression were analyzed. In anophthalmic patients who eventually underwent enucleation after PBRT due to disease progression, orbital volume (OV) was assessed from magnetic resonance (MR) images using the Pinnacle3 program. RESULTS: Among the six patients with PBRT history, three had uveal melanoma, and three children had retinoblastoma. Two eyes were treated with PBRT only, while the other four eyes ultimately underwent enucleation. Two eyes with PBRT only suffered from radiation dermatitis and intractable epiphora due to canaliculitis or punctal obstruction. All four anophthalmic patients showed severe enophthalmic features with periorbital hollowness. OV analysis showed that the difference between both orbits was less than 0.1 cm before enucleation, but increased to more than 2 cm³ after enucleation. CONCLUSION: PBRT for intraocular tumors can induce various orbital and periorbital tissue changes. More specifically, when enucleation is performed after PBRT due to disease progression, significant enophthalmos and OV decrease can develop and can cause poor facial cosmesis as treatment sequelae.

Effects on Periocular Tissues after Proton Beam Radiation Therapy for Intraocular Tumors

BACKGROUND: To present our experience on orbital and periorbital tissue changes after proton beam radiation therapy (PBRT) in patients with intraocular tumors, apart from treatment outcomes and disease control. METHODS: Medical records of 6 patients with intraocular tumors who had been treated with PBRT and referred to oculoplasty clinics of two medical centers (Seoul National University Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center) from October 2007 to September 2014 were retrospectively reviewed. The types of adverse effects associated with PBRT, their management, and progression were analyzed. In anophthalmic patients who eventually underwent enucleation after PBRT due to disease progression, orbital volume (OV) was assessed from magnetic resonance (MR) images using the Pinnacle3 program. RESULTS: Among the six patients with PBRT history, three had uveal melanoma, and three children had retinoblastoma. Two eyes were treated with PBRT only, while the other four eyes ultimately underwent enucleation. Two eyes with PBRT only suffered from radiation dermatitis and intractable epiphora due to canaliculitis or punctal obstruction. All four anophthalmic patients showed severe enophthalmic features with periorbital hollowness. OV analysis showed that the difference between both orbits was less than 0.1 cm before enucleation, but increased to more than 2 cm3 after enucleation. CONCLUSION: PBRT for intraocular tumors can induce various orbital and periorbital tissue changes. More specifically, when enucleation is performed after PBRT due to disease progression, significant enophthalmos and OV decrease can develop and can cause poor facial cosmesis as treatment sequelae.

Progression-free survival of children with localized ependymoma treated with intensity-modulated radiation therapy or proton-beam radiation therapy.

BACKGROUND: The treatment for childhood intracranial ependymoma includes maximal surgical resection followed by involved-field radiotherapy, commonly in the form of intensity-modulated radiation therapy (IMRT). Proton-beam radiation therapy (PRT) is used at some centers in an effort to decrease long-term toxicity. Although protons have the theoretical advantage of a minimal exit dose to the surrounding uninvolved brain tissue, it is unknown whether they have the same efficacy as photons in preventing local recurrence. METHODS: A retrospective review of medical records from September 2000 to April 2013 was performed. Seventy-nine children with newly diagnosed localized intracranial ependymomas treated with either IMRT (n = 38) or PRT (n = 41) were identified, and progression-free survival (PFS) was analyzed with Kaplan-Meier and Cox multivariate analyses. RESULTS: The median age at diagnosis was 3.7 years for all patients (range, 0.4-18.7 years). There were 54 patients with infratentorial tumors (68% of the total population). Patients treated with PRT were younger (median age, 2.5 vs 5.7 years; P = .001) and had a shorter median follow-up (2.6 vs 4.9 years; P < .0001). Gross total resection (GTR) was achieved in 67 patients (85%) and was more frequent in the PRT group versus the IMRT group (93% vs 76%; P = .043). The 3-year PFS rates were 60% and 82% with IMRT and PRT, respectively (P = .031). CONCLUSIONS: Children with localized ependymomas treated with PRT have a 3-year PFS rate comparable to that of children treated with IMRT. This analysis suggests that local control is not compromised by the use of PRT. The data also support GTR as the only prognostic factor for PFS. Cancer 2017;123:2570-78. © 2017 American Cancer Society.